Combining anti-inflammatory and anti-proliferative activities in ternary metal-NSAID complexes of a polypyridylamine ligand

To develop metallodrugs exhibiting anti-proliferative and anti-inflammatory activities, anti-proliferative supporting ligand and co-ligand NSAID were combined in ternary metal complexes. Three ternary complexes with the general formula [(TPA)M-II(diclofenac)](+) (TPA = tris(2-pyridylmethyl)amine, M = iron, cobalt and zinc) have been isolated and characterized. The crystal structure of the zinc(II)-diclofenac complex reveals a five-coordinate metal center, in which diclofenac coordinates in monodentate mode through one carboxylate oxygen. The iron(II) and zinc(II) complexes exhibit anti-proliferative effect on MDA-MB-231 human breast cancer cells with the IC(50 )value of 9.45 mu M and 9.00 mu M, respectively. On the contrary, the cobalt(II) complex shows less cytotoxicity due to its tendency toward oxidative degradation under aerobic conditions. The complexes display anti-inflammatory activity through inhibition of COX-pathways.